• Title/Summary/Keyword: Growth Background

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Increased Expression of Phospholipase C-$\gamma1$ Activator Protein, AHNAK in Human Lung Cancer Tissues (인체 폐암조직에서 Phospholipase C-$\gamma1$의 활성화 단백, AHNAK의 발현양상)

  • Oh, Yoon-Jung;Park, Chun-Seong;Choi, So-Yeon;Cheong, Seong-Cheoll;Lee, Sun-Min;Hwang, Sung-Chul;Lee, Yi-Hyeong;Hahn, Myung-Ho;Lee, Kyi-Beom;Ryu, Han-Young;Ha, Mahn-Joon;Bae, Yoon-Su;Rhee, Seo-Goo
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.347-355
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    • 1999
  • Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

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IP-10 Decreases TNF-α Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis (IP-10에 의한 기도상피세포에서의 TNF-α 유도 MUC5AC발현 억제: 특발성폐섬유증 환자의 적은 객담과의 연관성)

  • Kim, Seung Joon;Kang, Chun Mi;You, Moon Bin;Yoon, Hyung Kyu;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.5
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    • pp.347-355
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    • 2008
  • Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

A Case Study on the Growth of Learners through the Changemaker TEMPS Program (체인지메이커(Changemaker) TEMPS 프로그램을 통한 학습자의 성장에 대한 사례연구)

  • Kim, Nam Eun;Heo, Young Sun
    • Journal of Korean Home Economics Education Association
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    • v.31 no.3
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    • pp.91-116
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    • 2019
  • The purpose of this study is to examine the meaning of Changemaker education and to investigate the significance of Changemaker education in home economics education through a study of growth of learners applying the TEMPS program. To this end, first, the concept of Changemaker education was defined. Changemaker education is an education that changes society in a positive direction through a process of thinking about, learning about, making, and participating(playing) in various problems that we face in real life and drawing out solutions and share he solutions with others. Second, in this reasearch, the direction of Changemaker education is to make them interested in social problems and solve it and to make both the family and the career life happy and healthy by collaborating with other people. The scope of the contents is defined as "the selection of the content elements of the five domains of the child family, diet nutrition, clothing, housing and consumer life". As a way of teaching, we suggested that the TEMPS phase is followed so that the session purpose is achieved. Third, the Changemaker program consists of five steps of TEMPS among the five key ideas of Changemaker education. T(Thinking) is the step of understanding the problem and thinking about how to solve it, and E(Education) is getting the background for the next step. M(Making) is a step to create a target for problem solving, and P(Participation) and P(Play) are steps to Participation and enjoy. S(Share) is a step of changing the society through the result display, SNS sharing, and class presentation. In this study, 12 programs for middle school and 15 programs for high school were developed on the basis of TEMPS level. Each of the programs consists of 2 to 12 unit hours, which add up to 68 hours in the middle school program and 68 in high school. The learners who participated in the Changemaker program for one year (March 2, 2018~December 31, 2018) will experience improvement in many aspects including the linkage of life and education, practical ability, self-directed learning, self-esteem, sense of achievement and self-reflection, sensory observation, and so on.

Expression of EGFR in Non-small Cell Lung Cancer and its Effects on Survival (비소세포 폐암에서 EGFR의 발현률과 생존률에 미치는 영향)

  • Kim, Hak-Ryul;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.6
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    • pp.1285-1295
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    • 1997
  • Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

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The Present Situation and Challenges of the Russian Music Industry: Centered on the Digital Sound Sources (러시아 음악 산업 현황과 과제 - 디지털 음원을 중심으로 -)

  • Kwon, ki-bae;Kim, Se-il
    • Cross-Cultural Studies
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    • v.50
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    • pp.395-424
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    • 2018
  • The purpose of this paper is to examine the current situation and background of the Russian consumer music market, where digital music sources are making great strides in the noted recent years. In addition, music storage technology, media and change are considered together in this report. Moreover, Russia is the 12th largest music market in the world. The Russian music industry is following the recent trend of the global music industry, where the digital music market is growing rapidly on many different levels. The explosive growth of the digital sound sources in Russia's music industry is attributed to the explosive increase in available consumer downloads, streaming sound source service, and the increase in the number of digital sound sources using mobile technologies due to the development of the Internet. In particular, the sales of the available and accessible streaming sound sources are expected to grow explosively by the year 2020, which is expected to account for more than 85% of total digital music sales. In other words, the spread of smartphones and the resulting changes in the lifestyle of the Russians have created these changes for the global consumer of music. In other words, the time has come for anyone to easily access music and listen to music without a separate audio or digital player. And the fact that the Russian government's strong policy on the eradication of illegal copying of music is becoming an effective deterrent, as is also the factor that led to the increase of the share of the digital sound source to increase sales in Russia. Today, the Russian music industry is leading this change through the age and process of simply adapting to the digital age. Music is the most important element of cultural assets, and it is the beneficial content, which drives the overall growth of the digital economy. In addition, if the following five improvements(First, strengthen the consciousness of the Russian people about copyright protection; Second, utilizing the Big Data Internet resources in the digital music industry; Third, to improve the monopoly situation of digital music distributors; Fourth, distribution of fair music revenues; and Fifth, revitalization of a re-investment in the current Russian music industry) are effective and productive, Russia's role and position in the world music market is likely to expand.

Predictors of Latent Class of Longitudinal Medical Expenses of Older People and the Effects on Subjective Health (노인 의료비 변화궤적의 잠재계층 유형: 예측요인과 주관적 건강에 대한 영향)

  • Song, Si Young;Jun, Hey Jung;Choi, Bo Mi
    • 한국노년학
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    • v.39 no.3
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    • pp.467-484
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    • 2019
  • The purpose of this study is to explore latent classes of longitudinal medical expenses of older people and to analyze its predictors and its effects on subjective health. Among participants of the Korean Health Panel, the sample of this study includes 1,119 people who is 65-year-old or older and reported their medical expenses for nine consecutive years. The analyses were conducted in three steps. First, Growth Mixture Model (GMM) was applied to find distinct subgroups showing similar patterns in medical expenses. The results showed four groups which were classified as high medical expenditure maintenance group, medical expenditure increase group, low medical expenditure maintenance group, and medical expenditure reduction group. Second, the multinominal logistic regression found that the presence of spouse, economic participation, the number of chronic diseases, and the type of health insurance were significant predictors of latent classes in medical expenses. In particular, the greater the number of chronic diseases, the higher the likelihood of belonging to the high medical expenditure maintenance group. In addition, medical benefit recipients are more likely to belong to the low medical cost maintenance and medical cost reduction groups. Third, multiple regression analysis revealed that the older people in the groups with low or reducing expenses reported better subjective health than people with higher expenses. This study has its meanings in exploring the heterogeneity in longitudinal medical expenses among older people and its predictors and its associations with health outcome. The results of this research provide background information in establishing public health policy for older people.

Study on the effect of small and medium-sized businesses being selected as suitable business types, on the franchise industry (중소기업적합업종선정이 프랜차이즈산업에 미치는 영향에 관한 연구)

  • Kang, Chang-Dong;Shin, Geon-Chel;Jang, Jae Nam
    • Journal of Distribution Research
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    • v.17 no.5
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    • pp.1-23
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    • 2012
  • The conflict between major corporations and small and medium-sized businesses is being aggravated, the trickle down effect is not working properly, and, as the controversy surrounding the effectiveness of the business limiting system continues to swirl, the plan proposed to protect the business domain of small and medium-sized businesses, resolve polarization between these businesses and large corporations, and protect small family run stores is the suitable business type designation system for small and medium-sized businesses. The current status of carrying out this system of selecting suitable business types among small and medium-sized businesses involves receiving applications for 234 items among the suitable business types and items from small and medium-sized businesses in manufacturing, and then selecting the items of the consultative group by analyzing and investigating the actual conditions. Suitable business type designation in the service industry will involve designation with priority on business types that are experiencing social conflict. Three major classifications of the service industry, related to the livelihood of small and medium-sized businesses, will be first designated, and subsequently this will be expanded sequentially. However, there is the concern that when designated as a suitable business type or item, this will hinder the growth motive for small to medium-sized businesses, and designation all cause decrease in consumer welfare. Also it is highly likely that it will operate as a prior regulation, cause side-effects by limiting competition systematically, and also be in violation against the main regulations of the FTA system. Moreover, it is pointed out that the system does not sufficiently reflect reverse discrimination factor against large corporations. Because conflict between small to medium sized businesses and large corporations results from the expansion of corporations to the service industry, which is unrelated to their key industry, it is necessary to introduce an advanced contract method like a master franchise or local franchise system and to develop local small to medium sized businesses through a franchise system to protect these businesses and dealers. However, this method may have an effect that contributes to stronger competitiveness of small to medium sized franchise businesses by advancing their competitiveness and operational methods a step further, but also has many negative aspects. First, as revealed by the Ministry of Knowledge Economy, the franchise industry is contributing to the strengthening of competitiveness through the economy of scale by organizing existing individual proprietors and increasing the success rate of new businesses. It is also revealed to be a response measure by the government to stabilize the economy of ordinary people and is emphasized as a 'useful way' to revitalize the service industry and improve the competitiveness of individual proprietors, and has been involved in contributions to creating jobs and expanding the domestic market by providing various services to consumers. From this viewpoint, franchises fit the purpose of the suitable business type system and is not something that is against it. Second, designation as a suitable business type may decrease investment for overseas expansion, R&D, and food safety, as well negatively affect the expansion of overseas corporations that have entered the domestic market, due to the contraction and low morale of large domestic franchise corporations that have competitiveness internationally. Also because domestic franchise businesses are hard pressed to secure competitiveness with multinational overseas franchise corporations that are operating in Korea, the system may cause difficulty for domestic franchise businesses in securing international competitiveness and also may result in reverse discrimination against these overseas franchise corporations. Third, the designation of suitable business type and item can limit the opportunity of selection for consumers who have up to now used those products and can cause a negative effect that reduces consumer welfare. Also, because there is the possibility that the range of consumer selection may be reduced when a few small to medium size businesses monopolize the market, by causing reverse discrimination between these businesses, the role of determining the utility of products must be left ot the consumer not the government. Lastly, it is desirable that this is carried out with the supplementation of deficient parts in the future, because fair trade is already secured with the enforcement of the franchise trade law and the best trade standard of the Fair Trade Commission. Overlapping regulations by the suitable business type designation is an excessive restriction in the franchise industry. Now, it is necessary to establish in the domestic franchise industry an environment where a global franchise corporation, which spreads Korean culture around the world, is capable of growing, and the active support by the government is needed. Therefore, systems that do not consider the process or background of the growth of franchise businesses and harm these businesses for the sole reason of them being large corporations must be removed. The inhibition of growth to franchise enterprises may decrease the sales of franchise stores, in some cases even bankrupt them, as well as cause other problems. Therefore the suitable business type system should not hinder large corporations, and as both small dealers and small to medium size businesses both aim at improving competitiveness and combined growth, large corporations, small dealers and small to medium sized businesses, based on their mutual cooperation, should not include franchise corporations that continue business relations with them in this system.

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Effects of climate change on biodiversity and measures for them (생물다양성에 대한 기후변화의 영향과 그 대책)

  • An, Ji Hong;Lim, Chi Hong;Jung, Song Hie;Kim, A Reum;Lee, Chang Seok
    • Journal of Wetlands Research
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    • v.18 no.4
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    • pp.474-480
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    • 2016
  • In this study, formation background of biodiversity and its changes in the process of geologic history, and effects of climate change on biodiversity and human were discussed and the alternatives to reduce the effects of climate change were suggested. Biodiversity is 'the variety of life' and refers collectively to variation at all levels of biological organization. That is, biodiversity encompasses the genes, species and ecosystems and their interactions. It provides the basis for ecosystems and the services on which all people fundamentally depend. Nevertheless, today, biodiversity is increasingly threatened, usually as the result of human activity. Diverse organisms on earth, which are estimated as 10 to 30 million species, are the result of adaptation and evolution to various environments through long history of four billion years since the birth of life. Countlessly many organisms composing biodiversity have specific characteristics, respectively and are interrelated with each other through diverse relationship. Environment of the earth, on which we live, has also created for long years through extensive relationship and interaction of those organisms. We mankind also live through interrelationship with the other organisms as an organism. The man cannot lives without the other organisms around him. Even though so, human beings accelerate mean extinction rate about 1,000 times compared with that of the past for recent several years. We have to conserve biodiversity for plentiful life of our future generation and are responsible for sustainable use of biodiversity. Korea has achieved faster economic growth than any other countries in the world. On the other hand, Korea had hold originally rich biodiversity as it is not only a peninsula country stretched lengthily from north to south but also three sides are surrounded by sea. But they disappeared increasingly in the process of fast economic growth. Korean people have created specific Korean culture by coexistence with nature through a long history of agriculture, forestry, and fishery. But in recent years, the relationship between Korean and nature became far in the processes of introduction of western culture and development of science and technology and specific natural feature born from harmonious combination between nature and culture disappears more and more. Population of Korea is expected to be reduced as contrasted with world population growing continuously. At this time, we need to restore biodiversity damaged in the processes of rapid population growth and economic development in concert with recovery of natural ecosystem due to population decrease. There were grand extinction events of five times since the birth of life on the earth. Modern extinction is very rapid and human activity is major causal factor. In these respects, it is distinguished from the past one. Climate change is real. Biodiversity is very vulnerable to climate change. If organisms did not find a survival method such as 'adaptation through evolution', 'movement to the other place where they can exist', and so on in the changed environment, they would extinct. In this respect, if climate change is continued, biodiversity should be damaged greatly. Furthermore, climate change would also influence on human life and socio-economic environment through change of biodiversity. Therefore, we need to grasp the effects that climate change influences on biodiversity more actively and further to prepare the alternatives to reduce the damage. Change of phenology, change of distribution range including vegetation shift, disharmony of interaction among organisms, reduction of reproduction and growth rates due to odd food chain, degradation of coral reef, and so on are emerged as the effects of climate change on biodiversity. Expansion of infectious disease, reduction of food production, change of cultivation range of crops, change of fishing ground and time, and so on appear as the effects on human. To solve climate change problem, first of all, we need to mitigate climate change by reducing discharge of warming gases. But even though we now stop discharge of warming gases, climate change is expected to be continued for the time being. In this respect, preparing adaptive strategy of climate change can be more realistic. Continuous monitoring to observe the effects of climate change on biodiversity and establishment of monitoring system have to be preceded over all others. Insurance of diverse ecological spaces where biodiversity can establish, assisted migration, and establishment of horizontal network from south to north and vertical one from lowland to upland ecological networks could be recommended as the alternatives to aid adaptation of biodiversity to the changing climate.

The Effect of Nonspecific Endothelin-1 Receptor Blocker ($Bosentan^{(R)}$) on Paraquat Induced Pulmonary Fibrosis in Rat (Paraquat에 의한 백서의 폐섬유화증에서 비선택적 Endothelin-1 receptor blocker($Bosentan^{(R)}$)의 치료효과)

  • Jeong, Hye-Cheol;Jung, Ki-Hwan;Kim, Byung-Gyu;Lee, Seung-Heon;Kim, Min-Kyung;Kim, Chung-Yeul;Park, Sang-Myun;Lee, Sin-Hyung;Shin, Chol;Cho, Jae-Youn;Shim, Jae-Jeong;In, Kwang-Ho;Kim, Han-Gyum;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.2
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    • pp.182-195
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    • 2001
  • Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

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Analysis of 5-aza-2'-deoxycytidine-induced Gene Expression in Lung Cancer Cell Lines (폐암 세포주에서 5-aza-2'-deoxycytidine 처치에 의해 발현되는 암항원 유전자 분석)

  • 김창수;이해영;김종인;장희경;박종욱;조성래
    • Journal of Chest Surgery
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    • v.37 no.12
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    • pp.967-977
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    • 2004
  • Background: DNA methylation is one of the important gene expression mechanisms of the cell. When cytosine of CpG dinucleotide in promotor is hypomethylated, expression of some genes that is controlled by this promoter is altered. In this study, the author investigated the effect of DNA demethylating agent, 5-aza-2'-deoxycytidine (ADC), on the expressions of cancer antigen genes, MHC and B7 in 4 lung cancer cell lines, NCIH1703, NCIH522, MRC-5, and A549. Material and Method: After treatment of cell lines, NCIH1703, NCIH522, MRC-5 and A549 with ADC (1 uM) for 48 hours, RT-PCR was performed by using the primers of MAGE, GAGE, NY-ESO-1, PSMA, CEA, and SCC antigen gene. In order to find the optimal ADC treatment condition for induction of cancer antigen, we studied the effect of ADC treatment time and dose on the cancer antigen gene expression. To know the effect of ADC on the expression of MHC or B7 and cell growth, cells were treated with 1 uM of ADC for 72 hours for FACS analysis or cells were treated with 0.2, 1 or 5 uM of ADC for 96 hours for cell counting. Result: After treatment of ADC (1 uM) for 48 hours, the expressions of MAGE, GAGE, NY-ESO-1, and PSMA genes increased in some cell lines. Among 6 MAGE isotypes tested, and gene expression of MAGE-1, -2, -3, -4 and -6 could be induced by ADC treatment. However, CEA gene expression did not change and SCC gene expression was decreased by ADC treatment. Gene expression was generally induced 24 - 28 hours after ADC treatment and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC ADC teatment, and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC teatment in ADC-Free medium. Most gene expression could be induced at 0.2 uM of ADC, but gene expression increased dependently on ADC treatment dose. The expression of MHC and B7 was not increased by ADC treatment in all four cell lines, and the growth rate of 4 cell lines decreased significantly with the increase of ADC concentrations. Conclusion: Treatment of lung cancer cell lines with ADC increases the gene expression MAGE, GAGE and NY-ESO-1 that are capable of induction of cytotoxic T lymphocyte response. We suggest that treatment with 1 uM of ADC for 48 hours and then culturing in ADC-free medium is optimal condition for induction of cancer antigen. However, ADC has no effect on MHC and B7 induction, additional modification for increase of expression of MHC, B7 and cytokine will be needed for production of efficient cancer cell vaccine.